The effects of aging on the BTBR mouse model of autism spectrum disorder.
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2014
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Abstract
Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.
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Jasien, Joan M, Caitlin M Daimon, Rui Wang, Bruce K Shapiro, Bronwen Martin and Stuart Maudsley (2014). The effects of aging on the BTBR mouse model of autism spectrum disorder. Front Aging Neurosci, 6. p. 225. 10.3389/fnagi.2014.00225 Retrieved from https://hdl.handle.net/10161/12452.
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Joan Mary Jasien
Dr. Joan Mary Jasien is a Med‑Peds–trained child neurologist and neurodevelopmental disabilities specialist with board certification in Internal Medicine, Pediatrics, and Neurology. She completed her Med‑Peds residency followed by fellowship training in Child Neurology and Neurodevelopmental Disabilities before joining Duke University Medical Center.
She co‑founded and co‑directs the Children’s Cerebral Palsy–Related Conditions Clinic, the Adults with Cerebral Palsy–Related Conditions Clinic, and the Adults with Spina Bifida Clinic, and also serves as Co‑Director of the Children’s Spina Bifida Clinic. Together, these four programs form Duke’s multidisciplinary clinics for children and adults with spina bifida and cerebral palsy–related conditions. Her clinical expertise focuses on hyperkinetic movements and hypertonia in individuals with cerebral palsy and related conditions, as well as the overall cognition and functioning of individuals with spina bifida and cerebral palsy and related conditions.
Dr. Jasien’s research centers on neurological aging in individuals with spina bifida and on community engagement in research, with the goal of improving long‑term health outcomes across the lifespan.
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